Abstract

Intensification of induction and consolidation treatment in de novo AML lead to a continuous improvement of disease-free survival in the last 20 years. To increase dose-intensity during consolidation, patients in continued CR (n = 16) which did not qualify for allogeneic BMT, received busulfan/cyclophosphamide conditioning and peripheral blood stem cell transplantation (PBSCT) after double induction treatment with TAD (thioguanine, daunorubicin and AraC) and HAM (high-dose AraC and mitoxantrone) and an early consolidation with a second course of TAD. G-CSF treatment was started on day two after each chemotherapy as well as on the day of PBSCT. PBSC were collected after mobilization with HAM for back-up and after the second course of TAD for transplantation. PBSCT could be performed in all patients being in continued CR (1.33 × 106 CD34+ cells per kg (range 1.0 to 2.9 × 106); 1.38 × 105 CFU-GM/kg (range 0.14 to 2.8 × 105)) except one patient with persistent pancytopenia after the second course of TAD. A further mobilization with cyclophosphamide was necessary in three patients after the second course of TAD. Leukocyte counts of 109/1 were achieved within 10.4 days (range 8–12). In five cases the increase in thrombocyte counts was biphasic but remained stable > 100 × 109/1 after 59 days (range 16–92) in all patients. Severe toxicities (grade IV) were observed in 4 patients (peumonia 2 ×, pericarditis 1 ×, VOD 1 ×). One patient died of pneumonia. Relapse-free survival was 66% (95% confidence interval 58 to 74%) at a mean observation time of 27 months. Cytogenetically patients were found to be at good (n = 1) intermediate (n = 14) and high risk (n = 1). Of the four patients relapsing three only achieved CR after a second induction cycle, one was at high risk cytogenetically and two had an excessively high initial LDH level (> 1000 U/l). One patient developed a myelodysplastic syndrome. Thus, myeloablative chemotherapy with PBSCT has tolerable toxicity and may be performed routinely as consolidation treatment following TAD-HAM-TAD. The risk of relapse seems to be increased if achievement of CR is delayed. The observed relapse-free survival justifies a randomized trial with standard versus high-dose chemotherapy combined with the transplantation of in vivo purged PBSCs.